| GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone. | |
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MedLine Citation:
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PMID: 19943853 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent evidence showed that neurotransmitters are synthesised in glial cells, such as the Schwann cells, which form myelin sheaths in the PNS. While the presence of GABA type A (GABA-A) receptors has been previously demonstrated in these cells, the evidence of GABA synthesis remained still elusive. In an attempt to demonstrate the presence of GABA in rat Schwann cells, we adopted a strategy, using several integrated neurochemical, molecular as well as immunocytochemical approaches. We first demonstrated the presence of glutamic acid decarboxylase of 67 kDa (GAD67) in Schwann cells, a crucial enzyme of the GABA synthesis mechanism. Second, we demonstrated that GABA is synthesized and localized in Schwann cells. As the third step we showed that allopregnanolone (10 nM), a potent allosteric modulator of GABA-A receptors, stimulates GABA synthesis through increased levels of GAD67 in Schwann cells. Analysis of intracellular signalling mechanisms revealed that the protein kinase A pathway, through enhanced cAMP levels and cAMP response element binding protein phosphorylation, modulates the allosteric action of allopregnanolone at the GABA-A receptor in Schwann cells. Our findings are the first to demonstrate that this GABA mechanism is active in Schwann cells thus establishing new potential therapeutic targets to control Schwann cell biology, which may prove useful in the treatment of several neurodegenerative disorders. |
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Authors:
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Valerio Magnaghi; Arpad Parducz; Angelisa Frasca; Marinella Ballabio; Patrizia Procacci; Giorgio Racagni; Giambattista Bonanno; Fabio Fumagalli |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-27 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 112 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-09 Completed Date: 2010-03-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 980-90 Citation Subset: IM |
Affiliation:
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Department of Endocrinology, Physiopathology and Applied Biology, Universit? degli Studi di Milano, Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics
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pharmacology* Animals CREB-Binding Protein / metabolism Cells, Cultured Chromatography, High Pressure Liquid / methods Computational Biology / methods Cyclic AMP / metabolism Forskolin / pharmacology Gene Expression Regulation / drug effects* Glutamate Decarboxylase / genetics, metabolism Phosphorylation / drug effects Pregnanolone / pharmacology* RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Schwann Cells / drug effects*, metabolism Sciatic Nerve / cytology Signal Transduction / drug effects Time Factors Up-Regulation gamma-Aminobutyric Acid / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics; 0/RNA, Messenger; 128-20-1/Pregnanolone; 56-12-2/gamma-Aminobutyric Acid; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC 2.3.1.48/CREB-Binding Protein; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1; EC 4.1.1.15/glutamate decarboxylase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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